Scientists at the nation's leading research institutions are warning that continued uncertainty over federal funding could lead to a brain drain that will undermine the country's global status in medicine.

With funding at the National Institutes of Health stagnant since 2003 and other countries increasing research spending, some scientists have chosen to work overseas rather than endure what they expect will be a years-long wait for the grants they need to launch their careers in the United States.

Experts discussed the threat as federal agencies brace for $85 billion in across-the-board spending cuts known as sequestration. The reductions will begin Friday unless Congress and the White House reach a deal to delay them — an outcome that appears increasingly unlikely.

At the NIH, which is responsible for more than 80 percent of federal biomedical research funding, sequestration would take a $1.5 billion chunk out of a $31 billion budget. That could slow research on cancer, Alzheimer's and other illnesses, said the agency's director, Francis S. Collins.

It would also exacerbate funding challenges that many scientists already face.

"If you're talking to a young researcher who has lots of ideas and they hear that if you're willing to take your research to China or India or Brazil ... the support is much stronger, that sounds pretty appealing," Collins said. He described the problem of scientists leaving as "modest, but growing."

Funding for the NIH has remained mostly flat over the past decade as medical costs rose, reducing the agency's purchasing power by nearly 20 percent since 2003. The problem has affected about 325,000 scientists at research powerhouses, including Johns Hopkins Medicine and the University of Maryland School of Medicine, both of which rely on NIH grants.

The effective reductions meant that just 18 percent of researchers who applied for an NIH grant in 2012 received one, down from 30 percent in 2003. The average age of scientists receiving their first grant has risen from 34 in 1970 to 44 last year, according to NIH data.

Paul Matsudaira spent 24 years at the Massachusetts Institute of Technology before taking a job in 2009 running the Department of Biological Sciences at the National University of Singapore.

"Funding is getting tough, to the point that most U.S. researchers feel the granting review system is broken," the Seattle native said by email. "The sense is that if you get a grant, you're lucky."

Matsudaira, 60, said many factors informed his decision to leave. One was his concern that tighter budgets are forcing the NIH to award grants for less ambitious projects rather than forward-thinking, riskier science — the kind that is usually more likely to lead to breakthroughs.

In Singapore, he said, the research environment reminds him of how it used to be in the United States.

"There is a feeling of entrepreneurship, go-go, can do. There is the heady rush of taking a gamble," he said. "The grass is definitely greener on this side of the fence."

Japan spent about 3.5 percent of its gross domestic product on research and development last year, compared with 2.8 percent in the United States and 1.6 percent in China. But China, like Japan, has increased science spending over the past two years, while U.S. spending has remained flat. That includes spending by the government and private industry.

No one tracks how many scientists are leaving the United States and for what reasons. Despite dire warnings, officials at the NIH, the University of Maryland and a dozen advocacy groups struggled to identify scientists who had actually departed, though most eventually did find examples.

Four scientists interviewed for this article stressed that funding was only part of the reason for leaving. Many of the scientists who are leaving were born overseas and are returning to their native countries in part to be closer to family or because of complications with visas.

Biologist Bo Wen arrived at Hopkins in 2005 from Fudan University in Shanghai. Five years later, he returned to Fudan, where he now runs his own laboratory studying stem cell differentiation, or how cells become other types of cells. The research could lead to improvements in cell therapy and new drugs.

Wen, 38, said concerns over funding were about half the reason he returned to China, along with a desire to be nearer his family.

"It's really hard to get grants in the U.S., especially for foreigners like me," said Wen. "Scientists can't survive without grant money, [and] it is much easier for me to get research funding in China."

Opinions about the pervasiveness of the problem and whether the United States could reach a tipping point that might accelerate departures vary. Mary Woolley, president and CEO of Research!America, said the number of scientists leaving probably isn't big enough to support meaningful data, but she expects to see more evidence in coming years — particularly as those scientists begin publishing their work.

Paula E. Stephan, a professor at Georgia State University who studies the economics of science, agreed.

"The numbers haven't been huge," Stephan said. "It's a very plausible hypothesis [that] relative resources should affect where people work. But there's just not good national-level data to test that hypothesis."

But scientists who oversee laboratories and interact with postdoctoral researchers say the issue is coming up more and more.

Andrew Feinberg, director of the Center for Epigenetics at Hopkins, said he has spoken with many talented young researchers in his lab who have raised concerns about the instability of federal research dollars.

"I do hear this a lot, and I find it hard to believe it's not a major issue," Feinberg said. "People get a good score [on a grant application] and they still don't know whether they're going to get funded. I think that particularly hurts young people."

Carol Greider, director of the department of molecular biology and genetics at Hopkins, has warned for years that stagnant research funding is threatening the nation's reputation as a place scientists from around the world come to innovate.

Her department is working with about $16 million in NIH funding, she said. She said she recently decided against offering a job to a promising young researcher after reviewing her budget and considering the uncertainty of future funding.

Grieder and two colleagues shared the 2009 Nobel Prize for discovering the enzyme telomerase — a substance that plays a crucial role in the genetic life of cells and holds promise for developing treatments to fight cancer and age-related diseases.

At the time of the discovery, she was in her 20s.

"Breakthroughs come from young scientists, and this group is in jeopardy today," Greider said. "I'm not sure that in the current climate we have for research funding that I would actually have received funding to be able to do the work that led to the Nobel Prize."

The NIH, which has been based in Maryland since the late 1930s, supports about 18,000 jobs in the state, according to the U.S. Office of Personnel Management. Researchers funded by the agency have made major advances in medicine, pioneering the use of chemotherapy to treat cancer and cracking the human genome.

Collins, the agency's director, has been raising concerns about the economic and medical impact of sequestration for months, but he has offered few specifics about how the agency will juggle the cuts. It is not clear whether decisions about which grants could be trimmed or rejected have been made.

Documents released last week by the Senate Appropriations Committee, which is chaired by Maryland Sen. Barbara A. Mikulski, show that the Department of Health and Human Services expects it would reduce the size of current NIH grants and make "hundreds fewer awards" under sequestration.

Recognizing global competition, Congress doubled NIH funding over a five-year period that began in 1998. And the agency received a significant bump from President Barack Obama's economic recovery law in 2009 and 2010. But funding has fallen back to pre-stimulus levels.

Even if sequestration is avoided — or dealt with soon after it begins — the agency is likely to continue to wrestle with funding for years as Washington looks for ways to trim federal budget deficits. This week's deadline is only the latest in a series of budget standoffs that began in 2011.

In most cases, the resolutions have involved cuts.

"What biomedical research desperately needs is a stable trajectory," Collins said. "What we've had instead has been a roller coaster of ups and downs and mostly downs."

Biologist Paul Matsudaira spent more than two decades at MIT before taking a job in 2009 at the National University of Singapore. Research funding in Singapore, he said, is exciting — the way he recalls it used to be in the United States.

Bo Wen spent five years at Hopkins doing his postdoctoral work in cellular biology. Many factors went into his decision to return to Fudan University in China, but uncertainty about funding was an important one.